PROJECT SUMMARY - VDDRC PRECLINICAL MODELS OF DIGESTIVE DISEASES CORE The main objectives of the Preclinical Models of Digestive Diseases Core are to provide VDDRC investigators with access to non-invasive small animal imaging, organoid models, state-of-the art research immunohistochemistry, consultative services in interpretation of morphologic findings in animal models and human digestive diseases, construction of Tissue arrays, and laser capture microdissection (LCM). The Core has three components: the Preclinical Imaging Subcore, the GI Organoid Subcore and the Tissue Morphology Subcore. The expansion and modification of this Core now provides VDDRC investigators the opportunity to move nimbly from investigations utilizing non-invasive molecular imaging (Preclinical Imaging Subcore) and histology (Tissue Morphology Subcore), often in tandem, in tractable transgenic model systems of digestive diseases to mechanistic studies using novel organoid culture-based systems (GI Organoid Subcore). Fifty-one VDDRC members utilized services provided by this Core in the last funding period. Ex vivo studies that employ organoids will subsequently inform and guide new in vivo experimentation which will ultimately culminate in studies of clinical populations. Continually expanded services include access to a variety of molecular imaging probes specifically tailored for imaging GI disease in preclinical animal models, including NIR-based optical imaging reagents and translational imaging compounds labeled with positron emitting isotopes (PET). The Preclinical Imaging Subcore will support all major small animal imaging modalities including optical, SPECT, and PET methods for molecular imaging, as provided by the Center for Small Animal Imaging within the Vanderbilt University Institute of Imaging Science. The GI Organoid Subcore provides a unique service in promoting organoid production from both transgenic mouse models and human GI tissues. The Tissue Morphology Subcore provides research immunohistochemistry services for both human and animal intestinal tissue, construction of TMAs, and access to LCM. In addition, Dr. Washington, the Core Director, provides the necessary expertise for interpretation of the histologic findings obtained in these studies.